EP3300729B1 - Therapeutic compositions containing macitentan - Google Patents

Therapeutic compositions containing macitentan Download PDF

Info

Publication number
EP3300729B1
EP3300729B1 EP17191033.4A EP17191033A EP3300729B1 EP 3300729 B1 EP3300729 B1 EP 3300729B1 EP 17191033 A EP17191033 A EP 17191033A EP 3300729 B1 EP3300729 B1 EP 3300729B1
Authority
EP
European Patent Office
Prior art keywords
macitentan
pharmaceutically acceptable
compound
diphenylpyrazin
butoxy
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Revoked
Application number
EP17191033.4A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP3300729A1 (en
Inventor
Martine Clozel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Actelion Pharmaceuticals Ltd
Original Assignee
Actelion Pharmaceuticals Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=41346591&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP3300729(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Actelion Pharmaceuticals Ltd filed Critical Actelion Pharmaceuticals Ltd
Priority to PL17191033T priority Critical patent/PL3300729T3/pl
Priority to SI200932016T priority patent/SI3300729T1/sl
Priority to SM20190740T priority patent/SMT201900740T1/it
Publication of EP3300729A1 publication Critical patent/EP3300729A1/en
Application granted granted Critical
Publication of EP3300729B1 publication Critical patent/EP3300729B1/en
Priority to HRP20192204TT priority patent/HRP20192204T1/hr
Revoked legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5578—Eicosanoids, e.g. leukotrienes or prostaglandins having a pentalene ring system, e.g. carbacyclin, iloprost
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to a product containing macitentan, i.e. the compound of formula (I) below or a pharmaceutically acceptable salt of this compound, in combination with at least one compound having prostacyclin receptor (IP) agonist properties, as defined in the claims, or a pharmaceutically acceptable salt thereof, as well as this product for therapeutic use, simultaneously, separately or over a period of time, in the treatment of a disease wherein endothelin is involved, namely pulmonary hypertension.
  • a product containing macitentan i.e. the compound of formula (I) below or a pharmaceutically acceptable salt of this compound, in combination with at least one compound having prostacyclin receptor (IP) agonist properties, as defined in the claims, or a pharmaceutically acceptable salt thereof, as well as this product for therapeutic use, simultaneously, separately or over a period of time, in the treatment of a disease wherein endothelin is involved, namely pulmonary hypertension.
  • IP prostacyclin receptor
  • endothelin receptor antagonists including the compound of formula (I) and the use of said endothelin receptor antagonists in the treatment of various diseases wherein endothelin is involved (i.a. heart failure, angina pectoris, pulmonary and systemic hypertension and erectile dysfunction).
  • IP prostacyclin receptor
  • WO 2004/017993 describes the use of the endothelin receptor antagonist bosentan together with the prostacyclin receptor agonist epoprostenol sodium for treating pulmonary arterial hypertension.
  • IP prostacyclin receptor
  • a first subject of this invention relates thus to a product containing macitentan or a pharmaceutically acceptable salt thereof, and at least one (and preferably one) compound having prostacyclin receptor (IP) agonist properties, or a pharmaceutically acceptable salt thereof.
  • IP prostacyclin receptor
  • a further subject of this invention is a product containing macitentan or a pharmaceutically acceptable salt thereof, in combination with at least one (and preferably one) compound having prostacyclin receptor (IP) agonist properties, or a pharmaceutically acceptable salt thereof, for therapeutic use, simultaneously, separately or over a period of time, in the treatment of a disease wherein endothelin is involved.
  • IP prostacyclin receptor
  • Macitentan is the recommended INN for the compound of formula (I) and this name will therefore be used to designate the compound of formula (I) in the present patent application.
  • “Simultaneously” or “simultaneous”, when referring to a therapeutic use, means in the present application that the therapeutic use concerned consists in the administration of two or more active ingredients by the same route and at the same time.
  • “Separately” or “separate”, when referring to a therapeutic use, means in the present application that the therapeutic use concerned consists in the administration of two or more active ingredients at approximately the same time by at least two different routes.
  • Another therapeutic administration over a period of time consists in the administration over time of the two or more active ingredients of the combination using different frequencies of administration for each of the active ingredients, whereby at certain points in time simultaneous administrations of all the active ingredients of the combination take place whereas at some other points in time only part of the active ingredients of the combination may be administered (for example, in the case of a combination of macitentan with NS-304, the therapeutic administration over a period of time could be such that macitentan will be administered once a day whereas NS-304 will be administered twice a day).
  • disease wherein endothelin is involved is meant in particular hypertension, pulmonary hypertension (including pulmonary arterial hypertension), diabetic arteriopathy, heart failure, erectile dysfunction, angina pectoris or pulmonary fibrosis.
  • IP prostacyclin receptor
  • IP prostacyclin receptor
  • Specific examples of compounds having prostacyclin receptor (IP) agonist properties include treprostinil and its pharmaceutically acceptable salts, epoprostenol and its pharmaceutically acceptable salts, iloprost and its pharmaceutically acceptable salts, beraprost and its pharmaceutically acceptable salts, 2- ⁇ 4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy ⁇ - N -(methylsulfonyl)acetamide (NS-304) and its pharmaceutically acceptable salts, and ⁇ 4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy ⁇ acetic acid (MRE-269) and its pharmaceutically acceptable salts.
  • salts refers to non-toxic, inorganic or organic acid and/or base addition salts. Reference can be made to " Salt selection for basic drugs", Int. J. Pharm. (1986), 33, 201-217 .
  • any reference to macitentan or to a compound having prostacyclin receptor (IP) agonist properties is to be understood as referring also to the pharmaceutically acceptable salts thereof, as appropriate and expedient.
  • the product according to this invention will be such that macitentan and the compound having prostacyclin receptor (IP) agonist properties are intended for a therapeutic use which takes place simultaneously or over a period of time.
  • IP prostacyclin receptor
  • macitentan and the compound having prostacyclin receptor (IP) agonist properties will be intended to be administered simultaneously.
  • macitentan and the compound having prostacyclin receptor (IP) agonist properties will be intended to be administered over a period of time.
  • the period of time intended for the therapeutic use of a product according to this invention will be at least one week, and preferably at least one or more months (for example six months). This period of time may also be the whole life of the patient that receives the product.
  • administration of macitentan will be alternated with administration of a compound having prostacyclin receptor (IP) agonist properties, and the interval between such administration will not exceed two or three days (and more preferably not exceed one day).
  • IP prostacyclin receptor
  • the therapeutic administration over a period of time could be such that macitentan will be administered once a day whereas NS-304 will be administered twice a day.
  • the compound having prostacyclin receptor (IP) agonist properties will be selected from 2- ⁇ 4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy ⁇ - N -(methylsulfonyl)acetamide (NS-304) and its pharmaceutically acceptable salts, and ⁇ 4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy ⁇ acetic acid (MRE-269) and its pharmaceutically acceptable salts.
  • IP prostacyclin receptor
  • the compound having prostacyclin receptor (IP) agonist properties is 2- ⁇ 4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy ⁇ - N -(methylsulfonyl)acetamide (NS-304) or a pharmaceutically acceptable salt thereof.
  • the administration route of macitentan and that of the compound having prostacyclin receptor (IP) agonist properties is preferably the same.
  • the common administration route for macitentan and for the compound having prostacyclin receptor (IP) agonist properties will be the oral route.
  • a dose of 0.05 to 2 mg (and preferably 0.1 to 1 mg) of macitentan per kg of patient body weight and per day will be appropriate.
  • a dose of 0.5 to 30 ⁇ g (and preferably 1.5 to 15 ⁇ g) of compound having prostacyclin receptor (IP) agonist properties per kg of patient body weight given twice a day will be appropriate.
  • the disease intended to be treated by a product according to this disclosure will be selected from hypertension, pulmonary hypertension, diabetic arteriopathy, heart failure, erectile dysfunction, angina pectoris and pulmonary fibrosis. More preferably, the disease intended to be treated by a product according to this disclosure will be selected from hypertension and pulmonary hypertension.
  • the disease intended to be treated by a product according to this invention is pulmonary hypertension (and notably pulmonary arterial hypertension).
  • the invention also relates to a pharmaceutical composition containing, as active principles, macitentan or a pharmaceutically acceptable salt of this compound, in combination with at least one (and preferably one) compound having prostacyclin receptor (IP) agonist properties, as defined in the claims, or a pharmaceutically acceptable salt thereof, as well as at least one excipient.
  • a pharmaceutical composition containing, as active principles, macitentan or a pharmaceutically acceptable salt of this compound, in combination with at least one (and preferably one) compound having prostacyclin receptor (IP) agonist properties, as defined in the claims, or a pharmaceutically acceptable salt thereof, as well as at least one excipient.
  • IP prostacyclin receptor
  • Male Wistar rats are purchased from Harlan (Netherlands) and maintained under conditions in accordance with local guidelines (Basel-Landschaft cantonal veterinary office). All rats are housed in climate-controlled conditions with a 12:12 hour light:dark cycle, and had free access to chow and water.
  • a telemetry system is implanted under anaesthesia by inhalation of 2.5% isoflurane (in 70% O 2 + 30% N 2 O).
  • a pressure radio-frequency transmitter is implanted into the peritoneal cavity, and a sensing catheter is inserted in the pulmonary artery. The transmitter is sutured to the abdominal musculature and the skin is closed.
  • a receiver platform transforms the radio signal into digitized input, that is sent to a dedicated personal computer (Compaq, Deskpro). Pulmonary arterial blood pressure measurements are calibrated by using an input from an ambient pressure reference. Telemetry units are obtained from Data Sciences (St. Paul, MN, USA). Monocrotaline (MCT; Sigma Chemicals, St Louis, MO, USA) is administered as a single subcutaneous (sc) injection (60 mg/kg) in a volume of 3 ml/kg, and control age-matched rats receive an equal volume of saline.
  • sc subcutaneous
  • the animals are randomly assigned to experimental groups, and treatment is initiated within 24 h after MCT injection, for a duration of 4 weeks.
  • Macitentan and the compound having prostacyclin receptor (IP) agonist properties are administered by the oral route.
  • the effects of macitentan, the compound having prostacyclin receptor (IP) agonist properties and their combination on pulmonary arterial blood pressure are measured by collecting data at 5-minute intervals. Hourly means of pulmonary arterial pressure are calculated for each rat.
  • rats are sacrificed.
  • the heart is removed and weighed, and the ratio of organ weight to body weight (BW) is calculated.
  • the right ventricle (RV) and the left ventricle plus septum are separated and weighed; the ratio RV/BW is used as an index of right ventricular hypertrophy. The lower the ratio RV/BW, the stronger the effect of the item(s) tested for reducing right ventricular hypertrophy.
  • SHR spontaneously hypertensive rats
  • CHO cells stably expressing the human IP receptor are cultured in Ham's F-12 medium containing 10% fetal bovine serum in a humidified atmosphere of 95% air and 5% CO 2 at 37°C.
  • Cells are seeded at 1 x 10 5 cells/well in 24-well plates and cultured for 48 h. Following a wash and incubation with assay buffer for 1 h at 37°C, the cells are exposed to various concentrations of test compound in the presence of IBMX (500 ⁇ M). After removal of supernatant, the reaction is stopped by addition of 0.2 M perchloric acid.
  • Adherent cells are frozen for 2 h at -80°C and thawed to extract intracellular cAMP.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
EP17191033.4A 2008-08-13 2009-08-12 Therapeutic compositions containing macitentan Revoked EP3300729B1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
PL17191033T PL3300729T3 (pl) 2008-08-13 2009-08-12 Kompozycje terapeutyczne zawierające macitentan
SI200932016T SI3300729T1 (sl) 2008-08-13 2009-08-12 Terapevtski sestavki, ki vsebujejo macitentan
SM20190740T SMT201900740T1 (it) 2008-08-13 2009-08-12 Composizioni terapeutiche contenenti macitentan
HRP20192204TT HRP20192204T1 (hr) 2008-08-13 2019-12-06 Terapeutski sastavi koji sadrže macitentan

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IB2008053252 2008-08-13
EP09786912.7A EP2315587B1 (en) 2008-08-13 2009-08-12 Therapeutic compositions containing macitentan
PCT/IB2009/053553 WO2010018549A2 (en) 2008-08-13 2009-08-12 Therapeutic compositions containing macitentan

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
EP09786912.7A Division EP2315587B1 (en) 2008-08-13 2009-08-12 Therapeutic compositions containing macitentan
EP09786912.7A Division-Into EP2315587B1 (en) 2008-08-13 2009-08-12 Therapeutic compositions containing macitentan

Publications (2)

Publication Number Publication Date
EP3300729A1 EP3300729A1 (en) 2018-04-04
EP3300729B1 true EP3300729B1 (en) 2019-10-09

Family

ID=41346591

Family Applications (2)

Application Number Title Priority Date Filing Date
EP17191033.4A Revoked EP3300729B1 (en) 2008-08-13 2009-08-12 Therapeutic compositions containing macitentan
EP09786912.7A Revoked EP2315587B1 (en) 2008-08-13 2009-08-12 Therapeutic compositions containing macitentan

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP09786912.7A Revoked EP2315587B1 (en) 2008-08-13 2009-08-12 Therapeutic compositions containing macitentan

Country Status (30)

Country Link
US (3) US8809334B2 (enExample)
EP (2) EP3300729B1 (enExample)
JP (3) JP5764061B2 (enExample)
KR (1) KR101678699B1 (enExample)
CN (1) CN102099026B (enExample)
AR (1) AR073031A1 (enExample)
AU (1) AU2009280843B2 (enExample)
BR (1) BRPI0917661B8 (enExample)
CA (1) CA2731370C (enExample)
CY (2) CY1119826T1 (enExample)
DK (2) DK3300729T3 (enExample)
ES (2) ES2763176T3 (enExample)
HK (1) HK1253355B (enExample)
HR (2) HRP20171917T1 (enExample)
HU (2) HUE047767T2 (enExample)
IL (1) IL211143A0 (enExample)
LT (2) LT3300729T (enExample)
MA (1) MA32614B1 (enExample)
MX (1) MX350011B (enExample)
MY (1) MY178894A (enExample)
NO (1) NO2315587T3 (enExample)
NZ (1) NZ591601A (enExample)
PL (2) PL3300729T3 (enExample)
PT (2) PT2315587T (enExample)
RU (1) RU2519161C2 (enExample)
SI (2) SI3300729T1 (enExample)
SM (2) SMT201900740T1 (enExample)
TW (1) TWI446911B (enExample)
WO (1) WO2010018549A2 (enExample)
ZA (1) ZA201101900B (enExample)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2006290309B2 (en) 2005-09-12 2012-04-05 Actelion Pharmaceuticals Ltd. Stable pharmaceutical composition comprising a pyrimidine-sulfamide
MX2010001837A (es) 2007-08-17 2010-03-10 Actelion Pharmaceuticals Ltd Derivados de 4-pirimidinasulfamida.
JP5522030B2 (ja) 2008-02-28 2014-06-18 日本新薬株式会社 線維化抑制剤
NO2315587T3 (enExample) 2008-08-13 2018-03-24
JP6542128B2 (ja) 2013-01-11 2019-07-10 コルセア ファーマ インコーポレイテッド トレプロスチニルのプロドラッグ
US9505737B2 (en) 2013-01-11 2016-11-29 Corsair Pharma, Inc. Treprostinil derivative compounds and methods of using same
US9394227B1 (en) 2015-06-17 2016-07-19 Corsair Pharma, Inc. Treprostinil derivatives and compositions and uses thereof
US9643911B2 (en) 2015-06-17 2017-05-09 Corsair Pharma, Inc. Treprostinil derivatives and compositions and uses thereof
US9794795B1 (en) 2016-04-29 2017-10-17 Corning Optical Communications Wireless Ltd Implementing a live distributed antenna system (DAS) configuration from a virtual DAS design using an original equipment manufacturer (OEM) specific software system in a DAS
JP2020502121A (ja) 2016-12-14 2020-01-23 レスピラ セラピューティクス インコーポレイテッドＲｅｓｐｉｒａ Ｔｈｅｒａｐｅｕｔｉｃｓ，Ｉｎｃ． 肺高血圧症および他の肺障害の処置のための方法および組成物
AU2019339401B9 (en) * 2018-09-14 2022-11-03 Pharmosa Biopharm Inc. Pharmaceutical composition for controlled release of weak acid drugs and uses thereof
BR112021011999A2 (pt) * 2018-12-21 2021-09-08 Actelion Pharmaceuticals Ltd Composição farmacêutica para o tratamento de hipertensão arterial pulmonar
TW202042818A (zh) 2019-01-25 2020-12-01 瑞士商艾克泰聯製藥有限公司 用於治療慢性血栓性肺高血壓之醫藥組成物
US12485119B2 (en) 2019-11-29 2025-12-02 Actelion Pharmaceuticals Ltd Methods of treating pulmonary arterial hypertension
US11969424B2 (en) 2019-12-16 2024-04-30 Tenax Therapeutics, Inc. Levosimendan for treating pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF)
CA3240614A1 (en) 2021-12-31 2023-07-06 Stuart Rich Oral formulations of levosimendan for treating pulmonary hypertension with heart failure with preserved ejection fraction

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002053557A1 (en) 2000-12-18 2002-07-11 Actelion Pharmaceuticals Ltd Novel sulfamides and their use as endothelin receptor antagonists
WO2008026156A2 (en) 2006-08-29 2008-03-06 Actelion Pharmaceuticals Ltd Therapeutic compositions comprising a specific endothelin receptor antagonist and a pde5 inhibitor

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4539333A (en) * 1976-05-11 1985-09-03 Burroughs Wellcome Co. Prostacyclin, methods of using and method of making
DE2845770A1 (de) * 1978-10-19 1980-04-30 Schering Ag Neue prostacyclin-derivate und verfahren zu ihrer herstellung
JPS58124778A (ja) 1982-01-20 1983-07-25 Toray Ind Inc ５，６，７−トリノル−４，８−インタ−ｍ−フエニレンＰＧＩ↓２誘導体
US4683330A (en) 1984-03-08 1987-07-28 The Upjohn Company Interphenylene carbacyclin derivatives
CN1481244A (zh) * 2000-12-19 2004-03-10 Ĭ��ר���ɷ����޹�˾ 含有吡唑并[4,3-d]嘧啶和抗血栓形成剂、钙拮抗剂、前列腺素或前列腺素衍生物的药物制剂
DE10100426B4 (de) 2001-01-08 2006-04-06 Steag Hamatech Ag Verfahren und Vorrichtung zum Zusammenfügen von Substraten
TWI316055B (enExample) * 2001-04-26 2009-10-21 Nippon Shinyaku Co Ltd
WO2004017993A1 (en) * 2002-08-12 2004-03-04 Actelion Pharmaceuticals Ltd Combination of prostacyclin or prostacyclin analogues and endothelin receptor antagonists for the treatment of pulmonary arterial hypertension
BR0316724A (pt) * 2002-12-02 2005-10-18 Actelion Pharmaceuticals Ltd Compostos, uso de um ou mais compostos, e, processo para a fabricação de composições farmacêuticas
US20050101608A1 (en) * 2003-09-24 2005-05-12 Santel Donald J. Iloprost in combination therapies for the treatment of pulmonary arterial hypertension
TW200628467A (en) * 2004-11-11 2006-08-16 Actelion Pharmaceuticals Ltd Novel sulfamides
AU2006290309B2 (en) * 2005-09-12 2012-04-05 Actelion Pharmaceuticals Ltd. Stable pharmaceutical composition comprising a pyrimidine-sulfamide
US8541433B2 (en) * 2008-02-20 2013-09-24 Actelion Pharmaceuticals, Ltd. Combination comprising macitentan and paclitaxel for treating multi-drug resistant ovarian cancer
NO2315587T3 (enExample) 2008-08-13 2018-03-24

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002053557A1 (en) 2000-12-18 2002-07-11 Actelion Pharmaceuticals Ltd Novel sulfamides and their use as endothelin receptor antagonists
WO2008026156A2 (en) 2006-08-29 2008-03-06 Actelion Pharmaceuticals Ltd Therapeutic compositions comprising a specific endothelin receptor antagonist and a pde5 inhibitor

Non-Patent Citations (16)

* Cited by examiner, † Cited by third party
Title
"Pulmonary Hypertension", 1 January 2008, article HILL, ET AL: "chapter 16", pages: 337 - 338 , 344-345, and 354-358, XP055514018
"Pulmonary Hypertension", 1 January 2008, HUMANA, article HIRSCHTRITT TODD, ET AL: "Transitions and Combination Therapy for Pulmonary Arterial Hypertension", pages: 337 - 362, XP055783048
ANONYMOUS: " CIALIS 2.5 mg film-coated tablets (EU/1/02/237/001-005, 009)", EMA, 12 November 2002 (2002-11-12), XP093126297, Retrieved from the Internet <URL:https://www.ema.europa.eu/en/documents/product-information/cialis-epar-product-information_en.pdf> [retrieved on 20240201]
ANONYMOUS: " Revatio 20 mg film-coated tablets (EU/1/05/318/003)", EMA, 28 October 2005 (2005-10-28), XP093126310, Retrieved from the Internet <URL:https://www.ema.europa.eu/en/documents/product-information/revatio-epar-product-information_en.pdf> [retrieved on 20240201]
ANONYMOUS: "ADCIRCA 20 mg film-coated tablets (EU/1/08/476/007)", EMA, 1 October 2008 (2008-10-01), XP093126293, Retrieved from the Internet <URL:https://www.ema.europa.eu/en/documents/product-information/adcirca-epar-product-information_en.pdf> [retrieved on 20240201]
ANONYMOUS: "VIAGRA 25 mg film-coated tablets VIAGRA 50 mg film-coated tablets VIAGRA 100 mg film-coated tablets (EU/1/98/077/020-023)", EMA, 14 September 1998 (1998-09-14), XP093126305, [retrieved on 20240201]
GALIÈ NAZZARENO ET AL: "Comparative analysis of clinical trials and evidence-based treatment algorithm in pulmonary arterial hypertension", JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, ELSEVIER, NEW YORK, NY, vol. 43, no. 12, 16 June 2004 (2004-06-16), NEW YORK, NY, XP028883901, ISSN: 0735-1097, DOI: 10.1016/j.jacc.2004.02.038
HUMBERT MARC, SITBON OLIVIER, SIMONNEAU GERALD: "Treatment of pulmonary arterial hypertension.", NEW ENGLAND JOURNAL OF MEDICINE, THE - NEJM, MASSACHUSETTS MEDICAL SOCIETY, US, vol. 351, no. 14, 30 September 2004 (2004-09-30), US, pages 1425 - 1436, XP002565700, ISSN: 1533-4406, DOI: 10.1056/NEJMra040291
IGLARZ, ET AL: "Pharmacology of Macitentan, an Orally Active Tissue-targeting Dual Endothelin Receptor Antagonist", THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2 July 2008 (2008-07-02), pages 736 - 745, XP055514027
K. KUWANO, A. HASHINO, K. NODA, K. KOSUGI, K. KUWABARA: "A Long-Acting and Highly Selective Prostacyclin Receptor Agonist Prodrug, 2- -N-(methylsulfonyl)acetamide (NS-304), Ameliorates Rat Pulmonary Hypertension with Unique Relaxant Responses of Its Active Form, acetic Acid (MRE-269), on Rat Pulmonary Artery", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, WILLIAMS AND WILKINS CO., US, vol. 326, no. 3, US, pages 691 - 699, XP055505633, ISSN: 0022-3565, DOI: 10.1124/jpet.108.138305
KUWANO KEIICHI ET AL: "2-{4-[5,6-(Diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N- (methylsulfonyl) acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, WILLIAMS AND WILKINS CO., US, vol. 322, no. 3, 1 September 2007 (2007-09-01), US, pages 1181 - 1188, XP002670411, ISSN: 0022-3565, DOI: 10.1124/JPET.107.124248
KUWANO KEIICHI; HASHINO ASAMI; ASAKI TETSUO; HAMAMOTO TAISUKE; YAMADA TETSUHIRO; OKUBO KAORI; KUWABARA KENJI: "2-{4-[5,6-(Diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N- (methylsulfonyl) acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, WILLIAMS AND WILKINS CO., US, vol. 322, no. 3, 1 September 2007 (2007-09-01), US, pages 1181 - 1188, XP002670411, ISSN: 0022-3565, DOI: 10.1124/JPET.107.124248
LEVINE D J: "Diagnosis and management of pulmonary arterial hypertension: Implications for respiratory care", RESPIRATORY CARE, DAEDALUS ENTERPRISES, INC., UNITED STATES, vol. 51, no. 4, 1 January 2006 (2006-01-01), United States, pages 368 - 381, XP009096420, ISSN: 0098-9142
OMAR ALI ET AL: "Emerging therapies for pulmonary arterial hypertension", EXPERT OPINION ON INVESTIGATIONAL DRUGS, vol. 16, no. 6, 1 January 2007 (2007-01-01), pages 803 - 818, XP055505625
S.H.LEE, ET AL: "current treatment strategies for pulmonary arterial hypertension", JOURNAL OF INTERNAL MEDICINE, vol. 258, 1 January 2005 (2005-01-01), pages 199 - 215, XP055514056
SIDHARTA ET AL.: "Pharmacokinetics and Pharmacodynamics of the Endothelin-1 Receptor Antagonist ACT-064992 in Healthy Subjects", J CHEM PHARMACOL, 2007

Also Published As

Publication number Publication date
MY178894A (en) 2020-10-21
SMT201900740T1 (it) 2020-01-14
PL3300729T3 (pl) 2020-04-30
MX350011B (es) 2017-08-22
BRPI0917661A2 (pt) 2015-12-01
JP2015180683A (ja) 2015-10-15
JP2011530581A (ja) 2011-12-22
CN102099026A (zh) 2011-06-15
BRPI0917661B1 (pt) 2019-12-17
BRPI0917661B8 (pt) 2021-05-25
SI2315587T1 (en) 2018-04-30
US20110136818A1 (en) 2011-06-09
US9173881B2 (en) 2015-11-03
EP3300729A1 (en) 2018-04-04
ES2763176T3 (es) 2020-05-27
US20160022678A1 (en) 2016-01-28
EP2315587B1 (en) 2017-10-25
US20140329824A1 (en) 2014-11-06
PL2315587T3 (pl) 2018-03-30
HRP20192204T1 (hr) 2020-03-06
MA32614B1 (fr) 2011-09-01
HK1253355B (en) 2020-06-19
HUE047767T2 (hu) 2020-05-28
KR20110045006A (ko) 2011-05-03
HRP20171917T1 (hr) 2018-02-09
CY1122641T1 (el) 2021-03-12
JP5956025B2 (ja) 2016-07-20
AU2009280843B2 (en) 2015-03-05
US8809334B2 (en) 2014-08-19
DK2315587T3 (en) 2018-01-02
JP2015187148A (ja) 2015-10-29
WO2010018549A2 (en) 2010-02-18
JP5764061B2 (ja) 2015-08-12
AU2009280843A1 (en) 2010-02-18
AR073031A1 (es) 2010-10-06
NO2315587T3 (enExample) 2018-03-24
HUE036071T2 (hu) 2018-06-28
DK3300729T3 (da) 2020-01-20
ZA201101900B (en) 2012-08-29
CY1119826T1 (el) 2018-06-27
EP2315587A2 (en) 2011-05-04
PT3300729T (pt) 2020-01-20
MX2011001625A (es) 2011-03-29
CA2731370A1 (en) 2010-02-18
HK1253355A1 (en) 2019-06-14
TWI446911B (zh) 2014-08-01
IL211143A0 (en) 2011-04-28
US9597331B2 (en) 2017-03-21
KR101678699B1 (ko) 2016-11-23
RU2519161C2 (ru) 2014-06-10
CN102099026B (zh) 2012-08-29
CA2731370C (en) 2017-03-14
LT3300729T (lt) 2020-01-10
RU2011109084A (ru) 2012-09-20
LT2315587T (lt) 2018-01-10
JP5956026B2 (ja) 2016-07-20
TW201010985A (en) 2010-03-16
SMT201700592T1 (it) 2018-03-08
PT2315587T (pt) 2018-01-31
SI3300729T1 (sl) 2020-02-28
WO2010018549A3 (en) 2010-07-29
NZ591601A (en) 2012-12-21
ES2652590T3 (es) 2018-02-05

Similar Documents

Publication Publication Date Title
EP3300729B1 (en) Therapeutic compositions containing macitentan
TWI712409B (zh) 具有增進之治療指數的硝醯基予體
KR20080035608A (ko) 액상 제제
JP2021519764A (ja) 線維性疾患を処置する方法
US20200323892A1 (en) Methods for treatment using small molecule potassium-sparing diuretics and natriuretics
HK1157221B (en) Therapeutic compositions containing macitentan
HK1157221A (en) Therapeutic compositions containing macitentan
AU2019365117A1 (en) Sildenafil for use in the treatment of osteoarthritis
US7091249B2 (en) Drugs for spinal anesthesia
CN118021781A (zh) 小分子化合物在制备治疗或改善垂体泌乳素细胞衰老促进泌乳素分泌药物中的应用
JP2002326957A (ja) 慢性閉塞性肺疾患の治療方法

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN PUBLISHED

AC Divisional application: reference to earlier application

Ref document number: 2315587

Country of ref document: EP

Kind code of ref document: P

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

AX Request for extension of the european patent

Extension state: AL BA RS

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20181004

RBV Designated contracting states (corrected)

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20190319

REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 1253355

Country of ref document: HK

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AC Divisional application: reference to earlier application

Ref document number: 2315587

Country of ref document: EP

Kind code of ref document: P

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602009060128

Country of ref document: DE

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 1187986

Country of ref document: AT

Kind code of ref document: T

Effective date: 20191115

REG Reference to a national code

Ref country code: HR

Ref legal event code: TUEP

Ref document number: P20192204T

Country of ref document: HR

REG Reference to a national code

Ref country code: RO

Ref legal event code: EPE

REG Reference to a national code

Ref country code: FI

Ref legal event code: FGE

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

Effective date: 20200115

Ref country code: PT

Ref legal event code: SC4A

Ref document number: 3300729

Country of ref document: PT

Date of ref document: 20200120

Kind code of ref document: T

Free format text: AVAILABILITY OF NATIONAL TRANSLATION

Effective date: 20200108

REG Reference to a national code

Ref country code: NO

Ref legal event code: T2

Effective date: 20191009

REG Reference to a national code

Ref country code: SE

Ref legal event code: TRGR

REG Reference to a national code

Ref country code: NL

Ref legal event code: FP

REG Reference to a national code

Ref country code: SK

Ref legal event code: T3

Ref document number: E 33011

Country of ref document: SK

REG Reference to a national code

Ref country code: HR

Ref legal event code: T1PR

Ref document number: P20192204

Country of ref document: HR

REG Reference to a national code

Ref country code: EE

Ref legal event code: FG4A

Ref document number: E018517

Country of ref document: EE

Effective date: 20191219

REG Reference to a national code

Ref country code: GR

Ref legal event code: EP

Ref document number: 20200400043

Country of ref document: GR

Effective date: 20200318

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2763176

Country of ref document: ES

Kind code of ref document: T3

Effective date: 20200527

REG Reference to a national code

Ref country code: HU

Ref legal event code: AG4A

Ref document number: E047767

Country of ref document: HU

REG Reference to a national code

Ref country code: DE

Ref legal event code: R026

Ref document number: 602009060128

Country of ref document: DE

PLBI Opposition filed

Free format text: ORIGINAL CODE: 0009260

REG Reference to a national code

Ref country code: AT

Ref legal event code: UEP

Ref document number: 1187986

Country of ref document: AT

Kind code of ref document: T

Effective date: 20191009

PLBI Opposition filed

Free format text: ORIGINAL CODE: 0009260

PLAX Notice of opposition and request to file observation + time limit sent

Free format text: ORIGINAL CODE: EPIDOSNOBS2

REG Reference to a national code

Ref country code: FI

Ref legal event code: MDE

Opponent name: STADA-ARZNEIMITTEL AKTIENGESELLSCHAFT

Ref country code: FI

Ref legal event code: MDE

Opponent name: GENERICS (UK) LTD

Ref country code: FI

Ref legal event code: MDE

Opponent name: AERA A/S

26 Opposition filed

Opponent name: AERA A/S

Effective date: 20200706

REG Reference to a national code

Ref country code: EE

Ref legal event code: HC1A

Ref document number: E018517

Country of ref document: EE

REG Reference to a national code

Ref country code: FI

Ref legal event code: MDE

Opponent name: GENERICS (UK) LTD

Ref country code: FI

Ref legal event code: MDE

Opponent name: AERA A/S

Ref country code: FI

Ref legal event code: MDE

Opponent name: STADA-ARZNEIMITTEL AKTIENGESELLSCHAFT

26 Opposition filed

Opponent name: STADA-ARZNEIMITTEL AKTIENGESELLSCHAFT

Effective date: 20200709

Opponent name: GENERICS (UK) LTD

Effective date: 20200709

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20192204

Country of ref document: HR

Payment date: 20200806

Year of fee payment: 12

REG Reference to a national code

Ref country code: FI

Ref legal event code: MDE

Opponent name: STADA-ARZNEIMITTEL AKTIENGESELLSCHAFT

Ref country code: FI

Ref legal event code: MDE

Opponent name: GENERICS (UK) LTD

Ref country code: FI

Ref legal event code: MDE

Opponent name: AERA A/S

PLBB Reply of patent proprietor to notice(s) of opposition received

Free format text: ORIGINAL CODE: EPIDOSNOBS3

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

R26 Opposition filed (corrected)

Opponent name: AERA A/S

Effective date: 20200706

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

R26 Opposition filed (corrected)

Opponent name: STADA-ARZNEIMITTEL AKTIENGESELLSCHAFT

Effective date: 20200709

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20192204

Country of ref document: HR

Payment date: 20210812

Year of fee payment: 13

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

R26 Opposition filed (corrected)

Opponent name: GENERICS (UK) LTD

Effective date: 20200709

PLAB Opposition data, opponent's data or that of the opponent's representative modified

Free format text: ORIGINAL CODE: 0009299OPPO

R26 Opposition filed (corrected)

Opponent name: AERA A/S

Effective date: 20200706

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20192204

Country of ref document: HR

Payment date: 20220811

Year of fee payment: 14

TPAC Observations filed by third parties

Free format text: ORIGINAL CODE: EPIDOSNTIPA

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230525

PLCK Communication despatched that opposition was rejected

Free format text: ORIGINAL CODE: EPIDOSNREJ1

APBM Appeal reference recorded

Free format text: ORIGINAL CODE: EPIDOSNREFNO

APBP Date of receipt of notice of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA2O

APAH Appeal reference modified

Free format text: ORIGINAL CODE: EPIDOSCREFNO

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20192204

Country of ref document: HR

Payment date: 20230726

Year of fee payment: 15

APBM Appeal reference recorded

Free format text: ORIGINAL CODE: EPIDOSNREFNO

APBP Date of receipt of notice of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA2O

APBM Appeal reference recorded

Free format text: ORIGINAL CODE: EPIDOSNREFNO

APBP Date of receipt of notice of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA2O

APBQ Date of receipt of statement of grounds of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA3O

APBQ Date of receipt of statement of grounds of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA3O

APBQ Date of receipt of statement of grounds of appeal recorded

Free format text: ORIGINAL CODE: EPIDOSNNOA3O

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: PL

Payment date: 20240628

Year of fee payment: 16

REG Reference to a national code

Ref country code: HR

Ref legal event code: ODRP

Ref document number: P20192204

Country of ref document: HR

Payment date: 20240709

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: LU

Payment date: 20240726

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20240705

Year of fee payment: 16

APBU Appeal procedure closed

Free format text: ORIGINAL CODE: EPIDOSNNOA9O

REG Reference to a national code

Ref country code: DE

Ref legal event code: R103

Ref document number: 602009060128

Country of ref document: DE

Ref country code: DE

Ref legal event code: R064

Ref document number: 602009060128

Country of ref document: DE

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IS

Payment date: 20240709

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BG

Payment date: 20240717

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20240702

Year of fee payment: 16

Ref country code: FI

Payment date: 20240821

Year of fee payment: 16

Ref country code: MC

Payment date: 20240729

Year of fee payment: 16

Ref country code: LT

Payment date: 20240708

Year of fee payment: 16

Ref country code: HR

Payment date: 20240709

Year of fee payment: 16

Ref country code: IE

Payment date: 20240702

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GR

Payment date: 20240712

Year of fee payment: 16

Ref country code: DK

Payment date: 20240813

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20240701

Year of fee payment: 16

Ref country code: SM

Payment date: 20240730

Year of fee payment: 16

Ref country code: PT

Payment date: 20240808

Year of fee payment: 16

RDAF Communication despatched that patent is revoked

Free format text: ORIGINAL CODE: EPIDOSNREV1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: PATENT REVOKED

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 20240703

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20240702

Year of fee payment: 16

RDAG Patent revoked

Free format text: ORIGINAL CODE: 0009271

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 20240901

Year of fee payment: 16

Ref country code: ES

Payment date: 20240904

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CZ

Payment date: 20240724

Year of fee payment: 16

Ref country code: EE

Payment date: 20240703

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: AT

Payment date: 20240725

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CY

Payment date: 20240708

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: HU

Payment date: 20240729

Year of fee payment: 16

Ref country code: SI

Payment date: 20240715

Year of fee payment: 16

Ref country code: SK

Payment date: 20240712

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: LV

Payment date: 20240703

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: RO

Payment date: 20240726

Year of fee payment: 16

Ref country code: NO

Payment date: 20240809

Year of fee payment: 16

Ref country code: IT

Payment date: 20240710

Year of fee payment: 16

Ref country code: SE

Payment date: 20240702

Year of fee payment: 16

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: SK

Ref legal event code: MC4A

Ref document number: E 33011

Country of ref document: SK

Effective date: 20240918

REG Reference to a national code

Ref country code: LT

Ref legal event code: MM9A

Effective date: 20290812

27W Patent revoked

Effective date: 20240918

GBPR Gb: patent revoked under art. 102 of the ep convention designating the uk as contracting state

Effective date: 20240918

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: TR

Payment date: 20240723

Year of fee payment: 16

Ref country code: MT

Payment date: 20240823

Year of fee payment: 16

REG Reference to a national code

Ref country code: HR

Ref legal event code: PNEV

Ref document number: P20192204

Country of ref document: HR

REG Reference to a national code

Ref country code: EE

Ref legal event code: MF4A

Ref document number: E018517

Country of ref document: EE

Effective date: 20241119

REG Reference to a national code

Ref country code: AT

Ref legal event code: MA03

Ref document number: 1187986

Country of ref document: AT

Kind code of ref document: T

Effective date: 20240918

REG Reference to a national code

Ref country code: SE

Ref legal event code: ECNC

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: MK

Payment date: 20240704

Year of fee payment: 16